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PubMed2004

Three-dimensional conformal radiotherapy for localized prostate cancer in kidney transplant recipients.

BACKGROUND: This is the first report of graft function and prostate cancer control in renal transplant recipients subjected to modern conformal radiotherapy. METHODS: Eight kidney transplant recipients were treated with three-dimensional conformal radiotherapy. All patients but one were subjected to transitory hormonal deprivation. A three-dimensional radiotherapy-planning system (Pinnacle, Philips Medical System, Bothell, WA) was used to delineate anatomic contours on pretreatment computed tomography and for dose computation. The clinical target volume encompassed the prostate and was expanded with a 10-mm wide margin in all directions to obtain the planning target volume. The irradiation technique consisted of a nine-field arrangement delivering 70 Gy in 2-Gy fractions, with 18-MV photon beams. Biochemical recurrence was defined as two consecutive increases in prostate-specific antigen (>1.5 ng/mL). Graft function was monitored by creatinine clearance. Excretory profiles were assessed by furosemide-stimulated diethylenetriaminepentaacetic acid renography. All patients were subjected to hip magnetic resonance imaging to assess for avascular hip necrosis. RESULTS: After a mean follow-up of 28 months, two patients showed isolated biochemical recurrence and six patients remained free of recurrence. In seven patients with functional allografts, the creatinine clearance was unimpaired by treatment. However, significant obstruction of the terminal ureter was revealed in two patients by furosemide-stimulated diethylenetriaminepentaacetic acid renograms. The doses delivered to the uretero-neocystostomy were calculated to range from less than 20 Gy to more than 45 Gy depending on bladder repletion. CONCLUSIONS: Adequate cancer control was achieved at the expense of infraclinical ureteral obstruction. The doses delivered to the uretero-neocystostomy may be reduced by having a full bladder at the time of irradiation. No avascular hip necrosis was observed.

Aged↗

PubMed2005

Internal hernia after pancreas transplantation with enteric drainage: an unusual cause of small bowel obstruction.

BACKGROUND: Although complications involving leaking at the enteric anastomosis site, graft thrombosis, and intraabdominal abscess formation have been well documented after pancreas transplantation, the occurrence of small bowel obstruction in this setting has received scant attention. Although uncommon, intestinal obstruction after pancreas transplantation may have atypical etiologies. In this article, we will review three unusual cases of intestinal obstruction in pancreas transplant recipients. The value of computed tomographic (CT) enteroclysis in equivocal situations in the diagnosis of the obstruction is emphasized. METHODS: In this study, we reviewed the posttransplant course of all pancreas transplants performed between July 1, 2002 and June 1, 2004. We specifically focused on all patients that required reexploration for suspected small bowel obstruction at any time after transplantation. RESULTS: A total of 65 pancreas transplants were performed between July 1, 2002 and June 1, 2004. Pancreas graft survival was 97%, and patient survival was 98.5%. Five (7.7%) patients presented with mechanical small bowel obstruction, three of which were secondary to internal herniation of small intestine through a defect posterior to the pancreas allograft. All patients recovered well postsurgically. DISCUSSION: Small bowel obstruction is an uncommon complication after pancreas transplantation. CT enteroclysis in the evaluation of small bowel obstruction may assist the patient care decision-making process by providing information on the location and severity of the obstruction in the clinical situation where conventional abdominal CT and radiography are equivocal. Prompt detection of small bowel obstruction with early surgical intervention can minimize complications and preserve allograft function.

Adult↗

PubMed2005

Toxicity-sparing protocols using mycophenolate mofetil in renal transplantation.

The introduction of triple-therapy regimens that include a calcineurin inhibitor (CNI), steroids, and azathioprine greatly reduced the risk of acute rejection in renal transplantation. However, the long-term use of both CNIs and steroids is associated with serious toxicities that ultimately can impact patient/graft survival. Mycophenolate mofetil (MMF), a highly effective immunosuppressant with no known nephrotoxicity, has been shown to provide benefits in preserving long-term renal allograft function relative to azathioprine. For these reasons, MMF has become an integral component of toxicity-sparing maintenance regimens that seek to minimize patient exposure to CNIs and steroids. This paper provides an overview of current strategies for reducing the toxicities associated with these agents, which include both withdrawal and avoidance regimens with or without induction therapy. Data are accumulating that toxicity-sparing regimens involving MMF are safe and decrease the risk of side effects that accompany the use of CNIs and steroids. Future studies will determine how to best implement these regimens in the renal transplant population.

Adrenal Cortex Hormones↗

PubMed2006

Slowing the progression of chronic allograft nephropathy by conversion from cyclosporine to tacrolimus: a randomized controlled trial.

BACKGROUND: Chronic allograft nephropathy (CAN) is a multifactorial process with immunologic and nonimmunologic factors. Because tacrolimus (Tac) has been ascribed a beneficial effect on some of these factors when compared to cyclosporine A (CyA), a randomized controlled trial was conducted to investigate whether conversion from CyA to Tac can ameliorate the progression of renal dysfunction in kidney transplant recipients (KTR) with CAN. METHODS: Of the 46 patients with biopsy-proven CAN enrolled, 24 were converted from CyA to Tac, whereas 22 patients were maintained on CyA. Serum creatinine (SCrea), lipid profiles and an antihypertensive score (AHS) were determined after 3, 6 and 12 months. AHS is based on the total number and dosages of antihypertensive medications used. SCrea and AHS were additionally evaluated at 36 months. RESULTS: SCrea was decreased in the Tac group (Tac(baseline): 297 +/- 67 micromol/L; Tac(6): 261+/- 70 micromol/L, P < 0.001; Tac(12): 254 +/- 55 micromol/L, P < 0.001; Tac(36): 255 +/- 78 micromol/L, P = 0.235), whereas a significant increase of SCrea was detected in the CyA group (CyA(baseline): 279 +/- 77 micromol/L, CyA(12): 333 +/- 98 micromol/L, P < 0.001; CyA(36): 317 +/- 89 micromol/L, P < 0.001). Compared to CyA therapy, SCrea in the Tac group declined after 12 and 36 months (P = 0.011 and 0.048, respectively) as well as AHS (Tac(12): 59 +/- 13, CyA(12): 83 +/- 14, P < 0.001; Tac(36): 60 +/- 12, CyA(36): 84 +/- 14, P < 0.001). LDL cholesterol was lower in the Tac group after 12 months (Tac(12): 2.5 +/- 0.5 mmol/L, CyA(12): 3.5 +/- 0.6 mmol/L, P < 0.001). CONCLUSION: Conversion from CyA to Tac in KTR with CAN improves allograft function, lowers blood pressure, and reduces LDL cholesterol. This superior profile may translate into improved long-term graft survival.

Adult↗

PubMed2006

Postinfectious glomerulonephritis in renal allograft recipients.

Postinfectious glomerulonephritis (PIGN) is a rare etiology of de novo glomerulonephritis following kidney transplantation. To date, there have only been eight cases reported in the literature. We report an additional three patients transplanted at our institution between January 2000 and October 2004 who had clinical and pathologic findings consistent with posttransplant PIGN. All three patients were type 1 diabetics. One had received a cadaveric kidney transplant, one a simultaneous kidney-pancreas transplant, and the third a living related kidney transplant followed by a pancreas transplant. All patients were on triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil, and prednisone. In each case, an acute decline in allograft function developed in association with a known or suspected infectious process, and renal biopsies revealed an immune complex glomerulonephritis with features of PIGN. All regained renal function with treatment of their known or suspected infections and without specific therapies for their glomerulonephritis, including corticosteroids.

Adult↗

PubMed2006

Antibody and complement mediated injury in transplants following sensitization by allogeneic blood transfusion.

BACKGROUND: Many patients on the waiting list for transplants are sensitized from previous blood transfusions, pregnancy, or transplants. We investigated the role of complement in acute and chronic pathology in hearts transplanted to sensitized rats. METHODS: Blood was transfused from allogeneic PVG.R8 rats or control isogeneic PVG.1U rats to C6-sufficient and -deficient PVG.1U rats. Three weeks later hearts were transplanted from PVG.R8 donors and low-dose cyclosporin A was initiated. RESULTS: Allogeneic but not isogeneic blood transfusion elicited strong immunoglobulin (Ig) M, IgG1 and IgG2b alloantibody responses. Sensitization caused accelerated acute rejection of cardiac allografts by C6-sufficient recipients (4 days). In contrast, allografts functioned over 40 days in all C6-deficient recipients, but sensitization caused increased interstitial fibrosis and chronic vasculopathy. Circulating alloantibodies were associated with deposits of C4d on the vascular endothelium together with pericapillary accumulation of neutrophils and macrophages in the grafts. In contrast, T cells accumulated in periarterial lymphatics that did not have C4d deposits. CONCLUSIONS: Presensitization by allogeneic blood transfusion causes accelerated acute graft rejection in the presence of the complete complement cascade. In the absence of C6, macrophages colocalized with deposits of C4d and T cells accumulated in the periarterial lymphatics.

Animals↗

PubMed2006

Conversion from calcineurin inhibitors to sirolimus for chronic renal allograft dysfunction: a systematic review of the evidence.

BACKGROUND: Conversion from a calcineurin inhibitor to sirolimus has been used as a strategy to improve deteriorating renal allograft function but the efficacy and safety of this intervention is unknown. METHODS: We performed a systematic review of studies that involved conversion from a calcineurin inhibitor to sirolimus in kidney transplantation. The search yielded five randomized trials (n=1,040 patients) and 25 nonrandomized studies (n=977 patients). RESULTS: In the randomized trials, conversion to sirolimus improved short-term creatinine clearance (weighted mean difference 6.4 mL/min; 95% CI 1.9 to 11.0) compared to controls. In the nonrandomized studies, renal function improved or stabilized in 66% (95% CI 61% to 72%), creatinine clearance improved (weighted mean change 5.7 mL/min; 95% CI 1.4 to 10.1), cholesterol increased (weighted mean change 20.8 mg/dL; 95% CI 11.2 to 30.4) and triglycerides increased (weighted mean change 40.1 mg/dL; 95% CI 18.6 to 61.7). Sirolimus was discontinued by 28% of patients (95% CI 0 to 59%) in the randomized trials and 17% (95% CI 12 to 22%) in the nonrandomized trials. CONCLUSION: Conversion to sirolimus is associated with an improvement in short-term renal function. However, given the discontinuation rate and potential side effects, adequately powered randomized trials with longer follow-up of hard outcomes are needed to determine whether this strategy leads to a lasting benefit in the clinical care of transplant recipients.

Calcineurin Inhibitors↗

PubMed2004

GU evaluation and management of renal transplant candidates and recipients.

There are more than 200,000 end stage renal disease (ESRD) patients who are potential transplant candidates and more than 100,000 previously transplanted renal recipients with functioning allografts in the United States. Fifty-seven percent of these patients are male and forty percent are greater than 50 years of age. Diabetes is the most common cause of kidney failure. It is evident that many patients are at high risk for development of urologic problems and thus it is estimated that the average urologist will care for up to ten of these patients yearly. Thus a review of the genitourinary (GU) evaluation and management of these patients is timely.

Female Urogenital Diseases↗

PubMed1984

Tuberculosis of the colon in a kidney transplant patient.

A 58-year-old woman experienced recurrent fever episodes after kidney transplantation. She was treated with antibiotics because of suspicion of staphylococcus infection. Abdominal pain combined with haemorrhagic diarrhoea occurred eight months after transplantation. A barium enema revealed a stenotic process in the middle part of the ascending colon mimicking carcinoma, and hemicolectomy was consequently performed. Histological examination revealed tuberculosis with little granuloma formation and abundant acid-fast tubercle bacilli in the mucosa and submucosa, and only slight perigranulomatous reactions. The patient was successfully treated with triple antituberculous chemotherapy without deterioration of allograft function. Tuberculosis should be suspected in immunosuppressed patients suffering from pyrexia of unknown origin, even when chest X-ray is normal.

Colonic Diseases↗

PubMed1995

Cardiovascular and catecholamine response to surgery in brain-dead organ donors.

Eleven brain-dead organ donors were studied during surgery. Plasma levels of adrenaline and noradrenaline were measured before and after skin incision, upon sternotomy and 15, 30 and 45 min thereafter. Haemodynamic changes were measured continuously throughout the observation period. Blood pressure and heart rate increased after skin incision, remained high at sternotomy then decreased towards the end of the observation period in six of the 11 patients. Plasma catecholamines increased promptly with the onset of surgical stimuli. We conclude that surgical stress can evoke an excessive rise of plasma adrenaline and noradrenaline and thus could impair allograft function.

Adult↗

PubMed2001

Gastrointestinal infectious disease complications following transplantation and their differentiation from immunosuppressant-induced gastrointestinal toxicities.

It is often very difficult to distinguish between infection-related and immunosuppression-related gastrointestinal (GI) complications after transplantation. The risk of infection itself is determined by the patient's net state of immunosuppression as well as the presence of anatomic or technical abnormalities and the patient's epidemiological exposures. Of the anatomic abnormalities, diverticulitis is a particular problem in transplant patients, with a high rate of perforation and abscess formation. The causes of infectious disease syndromes are very different immediately after, early after, and late after transplantation. Infection during the first month may result from a pre-existing infection in the donor or recipient, or from the surgical wound, endotracheal tube, vascular access or drainage. During 1-6 months after transplantation, viruses attack and, with sustained immunosuppression, make opportunistic infections possible. Beyond 6 months after transplantation, the 80% of patients with good result from the transplant are at risk primarily for community-acquired microbes, including such enteric pathogens as Salmonella. Of the remaining patients, 10% have chronic viral infections and the 10% who have poor allograft function are at greatest risk for opportunistic infection. This time line is helpful in determining whether a GI complication is likely to be related to infection rather than a specific effect of an immunosuppressant drug. Fever, inflammatory cells in the stool, abnormalities on endoscopy or computed tomography and leukocytosis can be useful in the diagnosis but are inconsistent markers for an infectious cause.

Diagnosis, Differential↗

PubMed2005

Surgical considerations in the correction of valve dysfunction following heart transplantation.

Valve dysfunction is not an uncommon occurrence following heart transplantation but when present can be managed medically with diuretics and vasodilator therapy. If medical therapy fails, these patients are considered for retransplantation. Due to the scarcity of donor hearts, efforts aimed at limiting the pool of cardiac retransplantation candidates are being focused lately on preservation of cardiac allograft function by conventional operations in lieu of a retransplant. A review of the literature for patients who underwent valve operations following their heart transplants yielded 26 cases. Four of these had isolated mitral valve procedures, 18 had tricuspid procedures, two had combined mitral and tricuspid operations and two had aortic valve replacements. In this communication, we present a case of severe aortic insufficiency developing 7 yr after heart transplantation and leading to progressive clinical deterioration and NYHA class IV heart failure symptoms. The aortic valve was replaced with a 21-mm Carbo Medics supra-annular mechanical prosthesis (CarboMedics Inc.). She had a favorable postoperative course and remains well 7 months after her operation. Surgical correction of valvular lesions is warranted if the function of the previously transplanted heart is reasonably preserved.

Adult↗

PubMed1994

Immunosuppression of canine renal allograft recipients by CD4 and CD8 monoclonal antibodies.

A state of tolerance to MHC mismatched allografts can be generated in rodents by treatment with CD4 and CD8 monoclonal antibodies (mAb). In order to transpose this type of therapy to large animals and ultimately to the clinic, a suitable model is required. To this end we have generated a series of mAb to the canine CD4, CD8, and Thy-1 antigens and have tested their ability to prevent rejection of renal allografts. Donor-recipient pairs were selected from a colony of mongrel dogs in which untreated rejection of two haplotype-mismatched kidneys occurred by day 7 (defined as a serum creatinine > 300 mumol/l). Therapy with either the CD4 or the CD8 mAb, using no other immunosuppression, did not prolong graft survival. Depletion of T cells by a Thy-1 mAb prior to surgery only extended graft survival to day 9. However, treating with combinations of mAb up to day 10 (CD4 plus Thy-1; CD4 plus CD8; or CD4 plus CD8 plus Thy-1) prolonged renal allograft function up to 25 days. Combination of the triple mAb therapy with a sub-therapeutic immunosuppressive drug regimen (cyclosporin A plus azathioprine that alone gave a median survival of 15 days) favored survival to a median of 38 days. This protocol also inhibited the antiglobulin response that had curtailed the effects of mAb treatment, opening the way to more extended, and potentially tolerizing, mAb plus drug regimens.

Animals↗

PubMed2004

Lipid-based amphotericin in pulmonary zygomycosis: safety and efficacy of high exposure in a renal allograft recipient.

Zygomycosis is associated with a high mortality in immunosuppressed patients. Treatment typically includes surgical resection and administration of intravenous amphotericin B. Success of treatment may require withdrawal of immunosuppression, with risk of graft loss. We report the successful treatment of invasive pulmonary zygomycosis, following initial surgical resection, using very high doses of lipid-based amphotericin B without withdrawal of immunosuppression. The patient received daily doses up to 10 mg/kg/day (51 g cumulatively) of lipid-based amphotericin B along with a brief course of intrapleural amphotericin. Despite immunosuppression not being withdrawn, the patient's kidney allograft function remained stable. We conclude that high doses of lipid-based amphotericin B can be safe and effective as part of the treatment regimen for pulmonary zygomycosis.

Amphotericin B↗

PubMed2005

Prevalence and significance of anti-HLA and donor-specific antibodies long-term after renal transplantation.

Post-transplant circulating anti-human leukocyte antigens (HLA)-antibodies and C4d in allograft biopsies may be important in chronic rejection in renal transplant recipients (RTR). We determined the prevalence and significance of anti-HLA-antibodies and donor-specific antibodies (DSA). Sera were collected from 251 RTR >6 months post-transplant. Sera were tested using enzyme-linked immunosorbent assay (ELISA) screening for anti-HLA antibodies. Positive sera were retested with ELISA-specific panel for antibody specificity. A 11.2% of patients had anti-HLA antibodies and 4.4% had DSA. Anti-HLA antibodies were significantly associated with pretransplant sensitization, acute rejection and in multivariate analysis, higher serum creatinine (2.15 +/- 0.98 vs. 1.57 +/- 0.69 mg/dl in negative anti-HLA antibodies group). Allograft biopsies performed in a subset of patients with anti-HLA antibodies revealed that 66% had C4d in peritubular capillaries (0% in patients without antibodies). Anti-HLA antibodies were associated with a worse allograft function and in situ evidence of anti-donor humoral alloreactivity. Long-term RTR with an increase in creatinine could be screened for anti-HLA antibodies and C4d in biopsy.

Adolescent↗

PubMed1985

Coexistence of stomach cancer and renal adenoma in renal allograft. Clinical and autopsy findings and a review of previous cases in Japan.

Autopsy findings of a 34-year-old Japanese male with stomach cancer in a renal allograft are presented. The renal graft was given by his 53-year-old mother, who had the same HLA type as the patient and showed negative response in the Mixed Leukocyte Culture Reaction test. Stomach cancer occurred 4 years and 5 months after the renal graft, and infiltrated widely into the abdominal cavity, causing rectal stricture. In his original left kidney, a small renal adenoma was found. The tumor cells of the adenoma were composed of clear cells. In the adenoma, infiltration of stomach cancer was found. The renal allograft functioned very well until his death in spite of several rejection episodes. This is the seventh reported case in Japan in which a renal allotransplant was accompanied by malignancies.

Adenoma↗

PubMed1978

Calculi in renal transplants.

Three patients who underwent live donor renal transplantation subsequently developed calculi in their allografts. Hypercalcaemia and secondary hyperparathyroidism were present in 2 cases and these were treated by subtotal parathyroidectomy. Urinary stagnation and infection were contributory factors in the third case and reimplantation of the ureter was necessary. In all patients no further calculi have developed following treatment and allograft function remains satisfactory.

Adult↗

PubMed2005

Comparison of laparoscopic and open donor nephrectomy: UK experience.

UNLABELLED: A comparison of laparoscopic and open donor nephrectomy is presented by authors from the UK. They found that the laparoscopic approach could safely be offered to patients treated in experienced units and after adequate training fo the surgeon, with no increase in complications or decrease in efficacy. OBJECTIVE: To compare our early experience of laparoscopic donor nephrectomy (LDN) with a contemporary cohort of conventional open donor nephrectomy (ODN). PATIENTS AND METHODS: Transperitoneal left-sided LDN was offered to carefully selected potential live kidney donors on the basis of vascular anatomy. The first 20 donors who underwent LDN were compared with a control group of 20 patients who had ODN. Donors and recipients were compared for demographics, intraoperative variables, postoperative complications and allograft function. RESULTS: There was no peri-operative mortality in either group. No laparoscopic procedure required open conversion. The operating time was comparable (165 vs 153 min); LDN was associated with significantly less intraoperative blood loss (200 vs 350 mL; Mann-Whitney U, P = 0.01) and hospital stay (3 vs 5 days; P < 0.001). The graft warm ischaemic time was significantly longer for LDN (5 vs 2 min; P < 0.001) but this did not appear to affect either the delayed graft function rate (5% vs 10%, not significant) or serum creatinine level at discharge (125 vs 126 micromol/L). CONCLUSIONS: UK centres with experience of advanced laparoscopy and ODN can safely offer LDN to potential live donors.

Adult↗